Is isotretinoin safe to be administered to a patient with impaired renal function?

Fråga: Is isotretinoin safe to be administered to a patient with impaired renal function (estimated eGFR 53 mL/min)?

Sammanfattning: Elimination of isotretionoin is not strongly dependent on the kidney function. Therefore the risk of accumulation of isotretinoin when moderate dosages are administered to the patients with impaired renal function is not high. The current patient has a mild reduction of GFR, so the risk of accumulation of isotretinoin or its metabolites can be considered negligible, if therapeutic doses of isotretinoin will be given. It is notable that isotretionoin is teratogen and the patient should not get pregnant while she is treated with this agent.

Svar: Isotretinoin is a vitamin A derivative in the group retinoids. Isotretinoin is metabolized to several metabolites, and only a negligible amount of the parent drug is excreted unchanged in the urine (1, 2). Isotretinoin and its metabolites undergo glucuronidation before excretion to a similar extent in the urine and feces. In the intestine the hydrolyzed and glucuronide metabolites are reabsorbed (enterohepatic recirculation) (2, 3). The metabolites are 10 to 100-fold less potent than isotretinoin in vitro, therefore they are assumed to contribute to the pharmacological activity of the drug only slightly (2).

A prospective, randomized, single-blind study demonstrates the efficacy and safety of treatment of 20 patients with hemodialysis-related nodulocystic acne with isotretinoin 10 mg/day. However, two patients were excluded from the study because of isotretinoin-related side effects and toxic hepatitis. The authors conclude that isotretinoin may be the first choice of treatment of nodulocystic acne in this group of patients (4).

A case report explains treatment of diffuse and severe acne in a 32-year-old hemodialysis patient with a moderate dose of 20 mg (0.38 mg / kg) of isotretinoin per day. The treatment was effective and gave good result in 10 weeks without serious clinical side effects, apart from a transient increase in parathyroid hormone rate (5).

Two men and two women with chronic renal failure and no previous history of acne developed severe acne during dialysis. Anti-acne treatments (tetracyclines associated with local tretinoin in one case and oral isotreninoin in 3 cases) were well tolerated and resulted in complete regression of acne and pruritus and prurigo-like lesions (6). Lucek RW, Colburn WA. Clinical pharmacokinetics of the retinoids. Clin Pharmacokinet 1985;10(1):38-62 Vane FM, Bugge CJ, Rodriguez LC, Rosenberger M, Doran TI. Human biliary metabolites of isotretinoin: identification, quantification, synthesis, and biological activity. Xenobiotica 1990;20(2):193-207 Colburn WA, Gibson DM. Isotretinoin kinetics after 80 to 320 mg oral doses. Clin Pharmacol Ther 195;37(4):411-4 (abstract) Lin J, Shih I, Yu C. Hemodialysis-related nodulocystic acne treated with isotretinoin. Nephron 1999;81(2):146-150 Montagnac R, Reguiai Z, Bressieux JM, Schillinger F. Value of isotretinoin in the treatment of acne in hemodialysis patients: apropos of 1 case. Nephrologie 2003;24(2):101-5 (abstract) Grange F, Mitschler A, Genestier S, Guillaume JC. Severe pruriginous acne in dialysed renal failure. Diagnostic difficulties and efficacy of isotretinoin. Ann Dermatol Venereol 2001;128(11):1215-9 (abstract)